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Skewed repertoires have been linked to infections, vaccination responses and autoimmune diseases such as celiac disease (CeD) where biased usage of immunoglobulin and T-cell receptor genes reactive to disease relevant antigens has been reported. Motivated by evidence that germline variation, notably human leukocyte antigen (HLA), influences na\u00efve AIRRs and by prior machine-learning studies that classified CeD using na\u00efve BCR AIRR-sequencing (AIRR-seq) data, we applied machine learning analysis to na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    TCR and na\u00efve BCR AIRR-seq repertoires to test whether repertoire features can distinguish subjects with CeD from controls and to identify drivers of such classification. Na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    TCR repertoires yielded moderate diagnosis classification, but this signal was largely explained by enrichment of the HLA-DQ2.5 allotype. TCR variable gene frequencies predicted HLA-DQ2.5 status with high accuracy and controlling for HLA-DQ2.5 abolished TCR-based diagnosis classification. In contrast, na\u00efve BCR repertoires could not be used to classify CeD. Overall, our findings show that germline HLA variation significantly affects na\u00efve TCR composition and thereby indirectly facilitates moderately successful CeD status classification.\n                  <\/jats:p>","DOI":"10.1007\/s00251-026-01412-3","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T02:50:32Z","timestamp":1787799032000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Na\u00efve adaptive immune receptor repertoires in celiac disease assessed by machine learning; impact of the HLA-DQ2.5 allotype on the TCR repertoire"],"prefix":"10.1007","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6799-8751","authenticated-orcid":false,"given":"Aengus","family":"Officer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Lindeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Pavlovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin","family":"Lund-Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eivind","family":"Ness-Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geir Kjetil","family":"Sandve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"1412_CR1","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1136\/gutjnl-2024-333886","volume":"74","author":"IL Andersen","year":"2025","unstructured":"Andersen IL, Lukina P, Dyrli OT, Klaasen RA, Warren DJ, Bolstad N, Mj\u00f8nes P, R\u00f8nne E, Iversen R, Sollid LM, Lundin KEA, Ness-Jensen E (2025) Serological screening for coeliac disease in an adult general population: The HUNT study. 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